Severe Mitral Stenosis Secondary to Hunter’s Syndrome
A 25-year-old male was admitted to the emergency department for severe dyspnea (New York Heart Association Class IV). Physical examination revealed a short stature (139.5 cm), enlarged head, prominent supraorbital ridge, wide nasal bridge, flattened midface, thickened lips, macroglossia, short neck, claw hands, and umbilical hernia. The patient’s intelligence was normal. His sister informed us that he was diagnosed as having mucopolysaccharidosis (MPS) in infancy.
On hospital admission, chest radiography showed cardiomegaly with pulmonary edema. Electrocardiography showed sinus rhythm, biatrial abnormalities, and right ventricular hypertrophy (Figure 1). Laboratory tests were normal except for elevation of the level of B-type natriuretic peptide (2007 pg/mL). Transthoracic echocardiography demonstrated thickened mitral-valve leaflets, commissural fusion, and thickened subvalvular structures (Figure 2A and 2B; see Movies I and II in the online-only Data Supplement), resulting in severe mitral stenosis (MS; Figure 3A and 3B; the mitral-valve area measured by 2-dimensional planimetry, 0.6 cm2; the peak/mean transmitral pressure gradient, 47/27 mm Hg) and severe resting pulmonary hypertension (the tricuspid regurgitant jet velocity, 3.9 m/s; peak pressure gradient, 63 mm Hg). The anteroposterior dimension of the left atrium was 35 mm. Although the echocardiographic findings of MS were similar to rheumatic MS, we speculated that the cause of severe MS in this case could be the infiltration of glycosaminoglycans. Considering long-term survival of patients with a mild form of type II MPS, we undertook replacement of the mitral valve (St. Jude Medical, Minneapolis, MN; 25 mm; Figure 4) without complications. Histopathologic examination of the removed mitral valve showed abundant granules in foamy macrophages and interstitial spaces that were positive for periodic acid-Schiff stain and diastase sensitive (Figure 5). These findings confirmed that the cause of MS was infiltration of polysaccharides or mucosubstances instead of rheumatic involvement. During 1 year of follow-up, he has been in a stable condition and taken weekly enzyme replacement therapy after a definite diagnosis of type II MPS (Hunter’s syndrome) confirmed by deficient activity of iduronate-2-sulfatase in peripheral blood leukocytes.
MPS is a lysosomal storage disorder attributable to deficiency of the enzymes that degrade glycosaminoglycans.1 Hunter’s syndrome is a rare X-linked disorder characterized by a defect in enzyme iduronate-2-sulfatase that leads to the accumulation of glycosaminoglycans in nearly all cell types, tissues, and organs. This enzyme cleaves O-linked sulfate moieties from the glycosaminoglycans dermatan sulfate and heparan sulfate as the first step in their degradation pathway. Manifestations include severe airway obstruction, skeletal deformities, valvular abnormality, and, in most patients, neurological decline.2
Cardiac abnormalities detected by echocardiography are common in patients with Hunter’s syndrome. Valvular involvement, with thickening and stiffening of the valve leaflets, commonly leads to mitral and aortic regurgitation rather than stenosis.1
There are very rare cases of MS secondary to Hunter’s syndrome.1 Only 2 cases of successful mitral-valve replacement for MS secondary to Hunter’s syndrome have been reported:3,4 (1) a 28-year-old male,3 and (2) a 33-year-old male.4 They had a mild form of Hunter’s syndrome, as in our patient.
It is difficult to discriminate between rheumatic MS and MS secondary to MPS by echocardiographic findings of mitral-valve morphology. Diffuse and general thickening of the mitral valve and subvalvular structures, restrictive motion of whole mitral-valve leaflet, and a reduced degree of left atrial dilatation may suggest MS attributable to MPS rather than rheumatic MS.
We report here a patient with severe MS secondary to Hunter’s syndrome treated with mitral-valve replacement followed by enzymatic replacement therapy. This is the first case in whom the cause of MS secondary to Hunter’s syndrome was confirmed by histopathologic findings.
Sources of Funding
This work was supported for 2 years by a Pusan National University Research Grant (JKC).
The online-only Data Supplement is available with this article at http://circ.ahajournals.org/lookup/suppl/doi:10.1161/CIRCULATIONAHA.113.001688/-/DC1.
- © 2013 American Heart Association, Inc.
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- Scarpa M,
- Beck M,
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